The proto-oncogene, c-ets-2, of sea urchin (Lytechinus variegaths) has been molecularly cloned and sequenced. A comparison of the sequence of the c-ets-2 gene of sea urchin was made with the chicken retroviral homolog (v-ets) and the human cellular oncogen (Hu-ets-2). A remarkable conversation of these genes was noted; over 92% of the predicted amino acids of the sea urchin c-ets-2 was homologous to the viral oncogene. More than 94% of the predicted amino acids of sea urchin c-ets-2 matched with the human homolog Hu-ets-2; the highest homology thus far noted for such evolutionarily, widely-distributed oncogenes. The expression of messenger RNA was examined during sea urchin embryogenesis, using our cloned c-ets-2 DNA as a probe. It appears that the expression of the sea urchin c-ets-2 gene occurs early during embryonic development, peaking from 5 min to 17 hr post-fertilization, and declining markedly thereafter. The sea urchin mRNA identified by the cloned c-ets-2 probe was a unique species sized at 5.7-kb.